Download or read book Quantitative Estimation of P glycorptein mediated Drug Transport by Mechanistically Modeled Intrinsic Clearance written by Alex D. Morgan and published by . This book was released on 2015 with total page 262 pages. Available in PDF, EPUB and Kindle. Book excerpt: P-glycoprotein (P-gp/ ABCB1) is an important efflux drug transporter affecting the disposition of 50% of marketed drugs. Cell monolayer permeability assays are the gold sta ndard for assessing P-gp-drug interactions in vitro, but inter-laboratory assay differences produce heterogeneous results. We compared the validity and sensitivity of traditional assay metrics of efflux transport (unidirectional apparent permeability and efflux ratio) wi th a modeled clearance metric, CL P-gp and hypothesized that CL P-gp would be superior. Cell monolayers heterologously transfected with ABCB1, and 1,25(OH) 2 D 3 -modulated ABCB1 in cells served as experimental models. P-gp expression was quantified by western blot and bidir ectional [3 H]-digoxin transcellular flux was measured. Linear regression analys es were performed for P-gp expression versus each P-gp activity metric. The validity and sensitivi ty of modeled clearance was comparable to traditional metrics within a cell type, but wa s superior across different cell types. In conclusion, CL P-gp offers a physiologically-relevant and universally acceptable metric for efflux transport activity.
Download or read book Drug Transporters written by Martin F. Fromm and published by Springer Science & Business Media. This book was released on 2010-11-19 with total page 457 pages. Available in PDF, EPUB and Kindle. Book excerpt: It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.
Download or read book Principles of Clinical Pharmacology written by Arthur J. Atkinson Jr. and published by Elsevier. This book was released on 2011-04-28 with total page 567 pages. Available in PDF, EPUB and Kindle. Book excerpt: This revised second edition covers the pharmacologic principles underlying the individualization of patient therapy and contemporary drug development, focusing on the fundamentals that underlie the clinical use and contemporary development of pharmaceuticals. Authors drawn from academia, the pharmaceutical industry and government agencies cover the spectrum of material, including pharmacokinetic practice questions, covered by the basic science section of the certifying examination offered by the American Board of Clinical Pharmacology. This unique reference is recommended by the Board as a study text and includes modules on drug discovery and development to assist students as well as practicing pharmacologists. - Unique breadth of coverage ranging from drug discovery and development to individualization and quality assessment of drug therapy - Unusual cohesive of presentation that stems from author participation in an ongoing popular NIH course - Instructive linkage of pharmacokinetic theory and applications with provision of sample problems for self-study - Wide-ranging perspective of authors drawn from the ranks of Federal agencies, academia and the pharmaceutical industry - Expanded coverage of pharmacogenetics - Expanded coverage of drug transporters and their role in interactions - Inclusion of new material on enzyme induction mechanisms in chapters on drug metabolism and drug interactions - A new chapter on drug discovery that focuses on oncologic agents - Inclusion of therapeutic antibodies in chapter on biotechnology products
Download or read book Drug Discovery and Evaluation Methods in Clinical Pharmacology written by H.Gerhard Vogel and published by Springer Science & Business Media. This book was released on 2010-12-15 with total page 576 pages. Available in PDF, EPUB and Kindle. Book excerpt: Drug Discovery and Evaluation has become a more and more difficult, expensive and time-consuming process. The effect of a new compound has to be detected by in vitro and in vivo methods of pharmacology. The activity spectrum and the potency compared to existing drugs have to be determined. As these processes can be divided up stepwise we have designed a book series "Drug Discovery and Evaluation" in the form of a recommendation document. The methods to detect drug targets are described in the first volume of this series "Pharmacological Assays" comprising classical methods as well as new technologies. Before going to man, the most suitable compound has to be selected by pharmacokinetic studies and experiments in toxicology. These preclinical methods are described in the second volume „Safety and Pharmacokinetic Assays". Only then are first studies in human beings allowed. Special rules are established for Phase I studies. Clinical pharmacokinetics are performed in parallel with human studies on tolerability and therapeutic effects. Special studies according to various populations and different therapeutic indications are necessary. These items are covered in the third volume: „Methods in Clinical Pharmacology".
Download or read book A Pharmacology Primer written by Terry P. Kenakin and published by Academic Press. This book was released on 2018-10-26 with total page 489 pages. Available in PDF, EPUB and Kindle. Book excerpt: A Pharmacology Primer: Techniques for More Effective and Strategic Drug Discovery, Fifth Edition features the latest ideas and research regarding the application of pharmacology to the process of drug discovery. Written by well-respected pharmacologist, Terry P. Kenakin, this primer is an indispensable resource for all those involved in drug discovery. This updated edition has been thoroughly revised to include material on quantifying drug efficacy through bias and cluster analysis, the impact of molecular dynamics and protein structural analysis, the real time kinetic analysis of drug effect, virtual screening for new drug chemical scaffolds, and much more. With full color illustrations and new examples throughout, this book remains a top reference for all industry and academic scientists that is also ideal for students directly involved in drug discovery or pharmacologic research. Highlights changes surrounding strategies for drug discovery, providing a comprehensive reference and featuring advances in the methods involved Includes multiple new sections, such as development and utilization of models in pharmacology, de-orphanization of new drug targets, predicting impact of disease on drug pharmacokinetics, and the impact of enzyme kinetics on drug-drug interactions Illustrates the application of rapid inexpensive assays to predict activity in the therapeutic setting, showing data outcomes and the limitations inherent in interpreting this data
Download or read book Applied Clinical Pharmacokinetics written by Larry A. Bauer and published by McGraw Hill Professional. This book was released on 2007-09-22 with total page 842 pages. Available in PDF, EPUB and Kindle. Book excerpt: New sections on dosing strategies in all chapters. New chapter on sirolimus under the Immunosuppressants section. Essential information on drug dosing in special populations, including patients with renal and hepatic disease, obesity, and congestive heart failure. 30% of chapters extensively revised, others lightly updated
Download or read book Molecular Interaction Fields written by Gabriele Cruciani and published by John Wiley & Sons. This book was released on 2006-05-12 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: This unique reference source, edited by the world's most respected expert on molecular interaction field software, covers all relevant principles of the GRID force field and its applications in medicinal chemistry. Entire chapters on 3D-QSAR, pharmacophore searches, docking studies, metabolism predictions and protein selectivity studies, among others, offer a concise overview of this emerging field. As an added bonus, this handbook includes a CD-ROM with the latest commercial versions of the GRID program and related software.
Download or read book Oral Drug Absorption written by Jennifer B. Dressman and published by CRC Press. This book was released on 2016-04-19 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: Oral Drug Absorption, Second Edition thoroughly examines the special equipment and methods used to test whether drugs are released adequately when administered orally. The contributors discuss methods for accurately establishing and validating in vitro/in vivo correlations for both MR and IR formulations, as well as alternative approaches for MR an
Download or read book Transporters and Drug Metabolizing Enzymes in Drug Toxicity written by Albert P. Li and published by John Wiley & Sons. This book was released on 2021-07-27 with total page 530 pages. Available in PDF, EPUB and Kindle. Book excerpt: TRANSPORTERS AND DRUG-METABOLIZING ENZYMES IN DRUG TOXICITY Explore up-to-date coverage on the interaction between drug metabolism enzymes, transporters, and drug toxicity with this leading resources Transporters and Drug-Metabolizing Enzymes in Drug Toxicity delivers a comprehensive and updated review of the relationship between drug metabolism, transporters, and toxicity, providing insights into a major challenge in drug development – accurate assessment of human drug toxicity. Combining two disciplines frequently considered independently of one another, the book combines drug metabolism and toxicology with a focus on the role of biotransformation on drug toxicity and as a major factor for species and individual differences. Mechanism and species differences in drug metabolizing enzymes and transporters are discussed, as are the methods used to investigate the role of drug metabolizing enzymes and transporters in drug toxicity. Finally, the distinguished authors describe promising new experimental approaches to accurately assessing human drug toxicity via the consideration of human-specific drug metabolism in toxicity assays. In addition to topics as diverse as extended clearance models, experimental approaches for the estimation of DILI potential of drug candidates and roles of transporters in renal drug toxicity, readers will also enjoy the inclusion of such subjects as: A thorough overview of and introduction to drug metabolism and transporters and drug toxicity An exploration of drug metabolism enzymes and transporter activities as risk factors of marketed drugs associated with drug-induced fatalities A discussion of human-based in vitro experimental models for the evaluation of metabolism-dependent drug toxicity A treatment of mechanism-based experimental models for the evaluation of BSEP inhibition and DILI An examination of transporters and cochlea toxicity Perfect for scientists, students, and practitioners with interests in metabolism, toxicology, and drug development in the pharmaceutical industry, Transporters and Drug-Metabolizing Enzymes in Drug Toxicity will also earn a place in the libraries of medicinal chemists, pharmacologists, biochemists, toxicologists, and regulators in the pharmaceutical and health industries.
Download or read book Drug Bioavailability written by Han van de Waterbeemd and published by John Wiley & Sons. This book was released on 2006-03-06 with total page 602 pages. Available in PDF, EPUB and Kindle. Book excerpt: The peroral application (swallowing) of a medicine means that the body must first resorb the active substance before it can begin to take effect. The efficacy of drug uptake depends on the one hand on the chemical characteristics of the active substance, above all on its solubility and membrane permeability. On the other hand, it is determined by the organism's ability to absorb pharmaceuticals by way of specific transport proteins or to excrete them. Since many pharmacologically active substances are poorly suited for oral intake, a decisive criterion for the efficacy of a medicine is its so-called bioavailability. Written by an international team from academia and the pharmaceutical industry, this book covers all aspects of the oral bioavailability of medicines. The focus is placed on methods for determining the parameters relevant to bioavailability. These range from modern physicochemical techniques via biological studies in vitro and in vivo right up to computer-aided predictions. The authors specifically address possibilities for optimizing bioavailability during the early screening stage for the active substance. Its clear structure and comprehensive coverage make this book equally suitable for researchers and lecturers in industry and teaching.
Download or read book Handbook of Fluorescent Dyes and Probes written by R. W. Sabnis and published by John Wiley & Sons. This book was released on 2015-06-02 with total page 468 pages. Available in PDF, EPUB and Kindle. Book excerpt: A COMPLETE, UP-TO-DATE RESOURCE OF INFORMATION ON MORE THAN 150 FLUORESCENT DYES AND PROBES Handbook of Fluorescent Dyes and Probes is the most comprehensive volume available on the subject, covering all the available dyes and probes known to date in the literature for uses in various fields. Top dye expert Dr. Ram Sabnis organizes the compounds alphabetically by the most commonly used chemical name. He presents an easy-to-use reference complete with novel ideas for breakthrough research in medical, biological, chemical, color, material, physical and related allied fields. The ease of use of the handbook is further enhanced by various appendixes provided at the end of the book to conveniently and easily locate the dye as per the reader's need. This is the first book to give the CAS registry numbers, chemical structure, Chemical Abstract (CA) index name, all other chemical names, Merck Index number, chemical/dye class, molecular formula, molecular weight, physical form, solubility, melting point, boiling point, pKa, absorption maxima, emission maxima, molar extinction coefficient, and quantum yield of fluorescent dyes and probes, as well as to provide access to synthetic procedures (lab scale and industrial scale) of dyes and probes in a single source. This user-friendly handbook also features references on safety, toxicity and adverse effects of dyes and probes on humans, animals and the environment, including: acute/chronic toxicity aquatic toxicity carcinogenicity cytotoxicity ecotoxicity genotoxocity hematotoxicity hepatotoxicity immunotoxicity marine toxicity microbial toxicity mutagenicity nephrotoxicity neurotoxicity nucleic acid damage oral toxicity phototoxicity phytotoxicity reproductive toxicity skin toxicity Containing imaging/labeling applications, biological/medical applications and industrial applications, Handbook of Fluorescent Dyes and Probes is a convenient, vital resource for industrial and academic researchers, and a valuable desktop reference for medical professionals, lab supervisors, scientists, chemists, biologists, engineers, physicists, intellectual property professionals, students, and professors. Includes all fluorescent dyes & probes known to date and provides a complete, up-to-date library of information in one reference/handbook Includes more than 300 fluorescent dyes & probes organized alphabetically by the commonly used Chemical Name Provides access to synthesis procedures (lab scale and industrial scale) of fluorescent dyes & probes First book to provide references on safety, toxicity and adverse effects of fluorescent dyes and probes on humans, animals, and the environment User-friendly and convenient resource guide for chemical, biological, medical, and intellectual property professionals in a broad range of disciplines
Download or read book Comprehensive Medicinal Chemistry II written by David J Triggle and published by Elsevier. This book was released on 2006-12-29 with total page 9367 pages. Available in PDF, EPUB and Kindle. Book excerpt: The first edition of Comprehensive Medicinal Chemistry was published in 1990 and was very well received. Comprehensive Medicinal Chemistry II is much more than a simple updating of the contents of the first edition. Completely revised and expanded, this new edition has been refocused to reflect the significant developments and changes over the past decade in genomics, proteomics, bioinformatics, combinatorial chemistry, high-throughput screening and pharmacology, and more. The content comprises the most up-to-date, authoritative and comprehensive reference text on contemporary medicinal chemistry and drug research, covering major therapeutic classes and targets, research strategy and organisation, high-throughput technologies, computer-assisted design, ADME and selected case histories. It is this coverage of the strategy, technologies, principles and applications of medicinal chemistry in a single work that will make Comprehensive Medicinal Chemistry II a unique work of reference and a single point of entry to the literature for pharmaceutical and biotechnology scientists of all disciplines and for many industry executives as well. Also available online via ScienceDirect (2006) - featuring extensive browsing, searching, and internal cross-referencing between articles in the work, plus dynamic linking to journal articles and abstract databases, making navigation flexible and easy. For more information, pricing options and availability visit www.info.sciencedirect.com. Comprehensively reviews - the strategies, technologies, principles and applications of modern medicinal chemistry Provides a global and current perspective of today's drug discovery process and discusses the major therapeutic classes and targets Includes a unique collection of case studies and personal assays reviewing the discovery and development of key drugs
Download or read book Pharmacokinetics and Toxicokinetics written by Mehdi Boroujerdi and published by CRC Press. This book was released on 2015-02-24 with total page 538 pages. Available in PDF, EPUB and Kindle. Book excerpt: Pharmacokinetics and Toxicokinetics provides an overview of pharmacokinetics and toxicokinetics in a comprehensible, interrelated, and applied manner. It integrates the principles held in common by both fields through a logical and systematic approach. The book presents mathematical descriptions of physiological processes employed in different appr
Download or read book The Blood Brain Barrier BBB written by Gert Fricker and published by Springer. This book was released on 2014-10-24 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt: Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.
Download or read book Profiles of Drug Substances Excipients and Related Methodology written by Harry G. Brittain and published by Academic Press. This book was released on 2011-07-15 with total page 399 pages. Available in PDF, EPUB and Kindle. Book excerpt: Volumes in this widely revered series present comprehensive reviews of drug substances and additional materials, with critical review chapters that summarize information related to the characterization of drug substances and excipients. This organizational structure meets the needs of the pharmaceutical community and allows for the development of a timely vehicle for publishing review materials on this topic. The scope of the Profiles series encompasses review articles and database compilations that fall within one of the following six broad categories: Physical profiles of drug substances and excipients; Analytical profiles of drug substances and excipients; Drug metabolism and pharmacokinetic profiles of drug substances and excipients; Methodology related to the characterization of drug substances and excipients; Methods of chemical synthesis; and Reviews of the uses and applications for individual drug substances, classes of drug substances, or excipients. - Presents comprehensive reviews covering all aspects of drug development and formulation of drugs - Profiles creatine monohydrate and fexofenadine hydrochloride, as well as five others - Meets the information needs of the drug development community
Download or read book Drug Transport Across the Blood brain Barrier written by A.G. de Boer and published by CRC Press. This book was released on 1997-04-08 with total page 240 pages. Available in PDF, EPUB and Kindle. Book excerpt: The availability of various in vitro and in vivo techniques has considerably advanced the research on drug transport and metabolism across the blood-brain barrier (BBB). These specialized and sophisticated experimental strategies are of fundamental importance if one is to gain a greater understanding of enhanced and selective drug delivery to the brain. The reader will find in this book methods for in vitro endothelial/astrocyte cell culture models, and for in vivo intracerebral microdialysis to study drug tranport across the BBB. This book, however, is not merely a laboratory manual consisting of recipes for BBB research; it permits the presentation of the different methods in fine detail, revealing tricks and short cuts that frequently do not appear in the literature. The researcher is well aware that differences (subtle or otherwise) in experimental steps used in different laboratories may influence the outcome of any particular procedure. The book also illustrates the accessibility and the application of the different methods in different species. Background information of the protocol is given in every chapter, which also contains a literature list that the reader may wish to refer to for further information. This volume will be invaluable to basic researchers as well as to those involved in the search for agents suitable for pharmaceutic intervention in the central nervous system.
Download or read book Comprehensive Medicinal Chemistry III written by and published by Elsevier. This book was released on 2017-06-03 with total page 4609 pages. Available in PDF, EPUB and Kindle. Book excerpt: Comprehensive Medicinal Chemistry III, Eight Volume Set provides a contemporary and forward-looking critical analysis and summary of recent developments, emerging trends, and recently identified new areas where medicinal chemistry is having an impact. The discipline of medicinal chemistry continues to evolve as it adapts to new opportunities and strives to solve new challenges. These include drug targeting, biomolecular therapeutics, development of chemical biology tools, data collection and analysis, in silico models as predictors for biological properties, identification and validation of new targets, approaches to quantify target engagement, new methods for synthesis of drug candidates such as green chemistry, development of novel scaffolds for drug discovery, and the role of regulatory agencies in drug discovery. Reviews the strategies, technologies, principles, and applications of modern medicinal chemistry Provides a global and current perspective of today's drug discovery process and discusses the major therapeutic classes and targets Includes a unique collection of case studies and personal assays reviewing the discovery and development of key drugs
